Methods for modulating eicosanoid metabolism

ABSTRACT

The inventive subject matter relates to methods for treating prostate cancer, comprising administration of a composition comprising therapeutically effective amounts of supercritical extracts of rosemary, turmeric, oregano and ginger; and therapeutically effective amounts of hydroalcoholic extracts of holy basil, ginger, turmeric,  Scutellaria baicalensis , rosemary, green tea, huzhang, Chinese goldthread, and barberry.

BACKGROUND OF THE INVENTIVE SUBJECT MATTER

1. Field of the Inventive Subject Matter

The present inventive subject matter relates to novel methods fortreating prostate cancer, comprising administration of a compositioncomprising therapeutically effective amounts of supercritical extractsof rosemary, turmeric, oregano and ginger; and therapeutically effectiveamounts of hydroalcoholic extracts of holy basil, ginger, turmeric,Scutellaria baicalensis, rosemary, green tea, huzhang, Chinesegoldthread, and barberry.

2. Background

Prostate Cancer. Prostate cancer is the third most common cause of deathfrom cancer in men of all ages and is the most common cause of deathfrom cancer in men over 75 years old. Prostate cancer is rarely found inmen younger than 40. Men at higher risk include black men older than 60,farmers, tire workers, painters, and men exposed to cadmium. The lowestincidence occurs in Japanese men and vegetarians. The cause of prostatecancer is unknown, although some studies have shown a relationshipbetween high dietary fat intake or increased testosterone levels.

Prostate cancer is a serious and often life-threatening condition.Prostate cancer, which is characterized by rapidly-proliferating cellgrowth, continues to be the subject of worldwide research effortsdirected toward the identification of therapeutic agents which areeffective in the treatment thereof. Effective therapeutic agents prolongthe survivability of the patient, inhibit the rapidly-proliferating cellgrowth associated with the disease, or effect a regression of thedisease. Research in this area is primarily focused on identifyingagents which are therapeutically effective in humans and other mammals.

With prostate cancer, as with all solid tumors, it is the metastaticencroachment of the tumor on other vital function that causes the demiseof the patient. Approximately 10% of patients are diagnosed initiallywith metastatic disease. Ultimately, 30-40% of patients with this cancerwill develop metastatic disease. Once metastasis occurs, the cancerfollows a relentless progression unless interrupted by effectivetreatment. Prostate cancers are classified based on their aggressivenessand how different they are from the surrounding prostate tissue. Thereare several different ways to classify tumors; one of the more common isthe Whitmore-Jewett system, in which tumors are rated as follows:

-   -   A: tumor is unable to be felt on physical examination, and is        usually detected by accident after prostate surgery done for        other reasons.    -   B: tumor is confined to the prostate and usually detected by        physical examination or PSA testing.    -   C: extension of tumor beyond the prostate capsule without spread        to lymph nodes.    -   D: cancer has metastasized to regional lymph nodes or other        parts of the body, such as the bone and lungs for example.

With the advent of Prostate Specific Antigen (hereinafter “PSA”)testing, most prostate cancers are now found before they cause symptoms.The symptoms listed below are possible indicators of prostate cancer:urinary hesitancy, urinary dribbling, urinary retention, pain withurination, pain with ejaculation, lower back pain, pain with bowelmovement, excessive urination at night, incontinence, bone pain ortenderness, hematuria, abdominal pain, anemia, weight loss, andlethargy.

The appropriate treatment of prostate cancer is often controversial.Treatment options vary based on the stage of the tumor. In the earlystages, surgical removal of the prostate and radiation therapy may beused to eradicate the tumor. Metastatic cancer of the prostate may betreated by hormonal manipulation, reducing the levels of testosterone bydrugs or removal of the testes, or by chemotherapy.

Surgical removal of the prostate has several possible complications,including impotence and urinary incontinence. Removal of the testesalters hormone production and may be recommended for metastatic cancer,and has possible complications including loss of testosteroneproduction, leading to problems with sexual function, osteoporosis, andloss of muscle mass. Radiation therapy has possible complicationsincluding loss of appetite, fatigue, skin reactions such as redness andirritation, rectal burning or injury, diarrhea, cystitis, and blood inthe urine. Hormonal manipulation, which is mainly used to relievesymptoms without curing the prostate cancer, has possible complicationsincluding nausea and vomiting, hot flashes, anemia, lethargy,osteoporosis, reduced sexual desire, liver problems, diarrhea, enlargedbreasts, and erectile dysfunction, along with the obvious lack oftreatment of the disease itself. Chemotherapy, using medications such asmitoxantrone, prednisone, paclitaxel, docetaxel, estramustine, andadriamycin, has possible complications which are numerous and specificto a given chemotherapy drug.

Sufferers of prostate cancer often experience significant lifestylechanges, including disrupted sexual desire or performance on either atemporary or permanent basis; impotence; extensive monitoring forprogression of the disease; stress of illness; and urinary incontinence.Thus, there is a continuing need for alternative treatments for prostatecancer and for improved treatments for prostate cancer.

Cyclooxygenase Inhibitors. Cyclooxygenase is an enzyme-protein complexwith a variety of biochemical actions. There are at least three primaryCOX isoenzymes, COX-1, COX-2, and COX-3. COX-1 is a constitutive enzyme,produced at a reasonably consistent level at all times. It plays animportant role in, for example, gastrointestinal protection, kidneyfunction, and the aggregation of blood platelets. COX-2 production isnot constant; it varies depending on signals from various biochemicalcatalysts. For example, in the case of arthritis inflammation and pain,COX-2 responds to tissue damage by oxidizing arachidonic acid, creatingprostaglandins which in turn produce local inflammation. COX-3 has beenidentified relatively recently (Chandrasekharan, et al., PNAS U.S.A.,99(21):13926-31 (2002)). In humans, COX-3 mRNA is expressed mostabundantly in the cerebral cortex and heart tissues. COX-3 activity isselectively inhibited by analgesic/antipyretic drugs. It has beensuggested that inhibition of COX-3 could represent a mechanism by whichthese drugs decrease pain and possibly fever.

Prostaglandins play a major role in the inflammatory process and theinhibition of prostaglandin production, especially production of PGG₂,PGH₂, and PGE₂, has been a common target of anti-inflammatory drugdiscovery. However, common non-steroidal anti-inflammatory drugs(hereinafter “NSAIDs”) that are active in reducing theprostaglandin-induced pain and swelling associated with the inflammationprocess are also active in affecting other prostaglandin-regulatedprocesses not associated with the inflammation process.

NSAIDs have been found to prevent the production of prostaglandins byinhibiting enzymes in the human arachidonic acid/prostaglandin pathway,including the cyclooxygenase enzymes. Traditional non-steroidalanti-inflammatory drugs, such as aspirin, work by inhibiting both COX-1and COX-2. Thus, non-specific NSAIDs can have a damaging effect on thegastrointestinal tract, kidneys, and liver; blocking COX-1 can make thestomach lining more vulnerable, and reduced thromboxane production thinsthe blood, making gastrointestinal hemorrhage more likely, and may causeinadequate regulation of cellular immune functions and the secretion ofvarious cytokines. The use of high doses of most common NSAID's canproduce severe side effects, including life threatening ulcers, thatlimit their therapeutic potential.

COX-2 is associated with inflammation and provides a viable target ofinhibition which more effectively reduces inflammation and producesfewer and less drastic side effects. Thus, researchers have beenmotivated to develop selective COX-2 inhibitors to reduce inflammationand relieve pain without the gastrointestinal damage brought on byinhibiting COX-1. In addition, the current scientific understanding inthe art suggests that COX-2 inhibition may serve an important functionin promoting normal cell growth in the colon, pancreas, breast tissue,and other organ systems.

Some compounds which selectively inhibit cyclooxygenase-2 have beendescribed in U.S. Pat. Nos. 5,380,738, 5,344,991, 5,393,790, 5,434,178,5,474,995, 5,510,368 and WO documents WO96/06840, WO96/03388,WO96/03387, WO96/25405, WO95/15316, WO94/15932, WO94/27980, WO95/00501,WO94/13635, WO94/20480, and WO94/26731.

Drugs such as valdecoxib, celecoxib, and rofecoxib are intended toselectively inhibit COX-2 with minimal effect on COX-1. However, despitethe emphasis on COX-2 inhibition, even these drugs appear to haveserious long term side effects, such as the breakdown in digestiveprotective mucus and prevention of normal healing processes. There isthus a continuing need for more specific and non-specific COX-2inhibitors which avoid side effects associated with COX-1 inhibition.

Natural COX-2 Inhibitors. Several herbs have been found to inhibit theCOX-2 enzyme. For example, holy basil has been found to possesssignificant anti-inflammatory properties and is capable of blocking boththe cyclooxygenase and lipoxygenase pathways of arachidonate metabolism.Ursolic acid and oleanolic acid, two of the recognized phytonutients ofholy basil, have been found to have a significant COX-2 inhibitoryeffect.

Similarly, shogaols and gingerols, pungent components of ginger, havebeen found to inhibit cyclooxygenase. Eugenol, another activeconstituent of several medical herbs, has also been found to be a5-lipoxygenase inhibitor and to possess potent anti-inflammatory and/oranti-rheumatic properties.

Scutellaria baicalensis also has been found to inhibit the COX-2 enzyme.According to the USDA database, green tea contains six constituentshaving cyclooxygenase-inhibitor activity. According to the Napralertdatabase, green tea contains fifty one constituents havinganti-inflammatory activity. The polyphenols in green tea were found tocause a marked reduction in COX-2. Flavan-3-ol derivatives (+)-catechin,also present in green tea, have been reported to be COX-1 and COX-2inhibitors. In addition, salicylic acid, another constituent of greentea, also has been found to be a COX-2 inhibitor.

Berberine, found in barberry and Chinese goldthread, has also been foundto inhibit COX-2 without inhibiting COX-1 activity.

In U.S. Pat. No. 6,387,416, Applicants disclosed the inventivecompositions and their use for reducing inflammation. The contents ofU.S. Pat. No. 6,387,416 are hereby incorporated by reference in theirentirety. Surprisingly, as discussed in greater detail below, it hasbeen determined that the inventive compositions are useful for treatingprostate cancer as well.

Use of COX-2 Inhibitors for Treating Cancer. It has been postulated thatCOX-2 inhibitors may be useful for treating cancer. Yet only a very fewpatents actually disclose the use of COX-2 inhibitors for treating anycancers. In U.S. Pat. No. 5,466,823 to Talley, et al.,(Pyrazol-1-yl)benzene sulfonamides are disclosed as inhibitors ofcyclooxygenase-2, and for use in the treatment of inflammation,arthritis, and pain, and as being useful for preventing colon cancer.However, their use for actually treating colon cancer or for treating orpreventing other neoplasias is not disclosed.

U.S. Pat. No. 6,469,040 to Seibert, et al., discloses a method of usinga specific, disclosed class of cyclooxygenase-2 inhibitor derivatives inpreventing and treating epithelial cell neoplasia in a subject.

U.S. Pat. No. 6,534,540 to Kindness, et al., discloses a combination ofthe proprietary HMG-CoA reductase inhibitor lovastatin and theproprietary COX-2 inhibitor rofecoxib for the treatment of cancer,especially prostate cancer, and a method of treatment of cancer,especially prostate cancer, by that combination.

Based on the limited body of art disclosing the use of COX-2 inhibitorsfor treating any cancer, and the need for effective treatments forprostate cancer in particular, it is apparent that there is a great andimmediate need for new COX-2 inhibitors for treating prostate cancer.This need is met by the inventive methods and compositions, which treatprostate neoplasias without significant side effects.

SUMMARY OF THE INVENTIVE SUBJECT MATTER

The present inventive subject matter relates to a method for treatingprostate neoplasia in a subject, comprising the step of administering aneffective amount of a composition to said subject to treat or preventsaid prostate neoplasia, said composition comprising therapeuticallyeffective amounts of supercritical extracts of rosemary, turmeric,oregano and ginger; and therapeutically effective amounts ofhydroalcoholic extracts of holy basil, ginger, turmeric, Scutellariabaicalensis, rosemary, green tea, huzhang, Chinese goldthread, andbarberry, provided that said prostate neoplasia is not prostaticintraepithelial neoplasia.

The present inventive subject matter further relates to a method fortreating at least one cancerous tumor of the prostate in a subject,comprising the step of administering an effective amount of acomposition to said subject to treat said tumor, said compositioncomprising therapeutically effective amounts of supercritical extractsof rosemary, turmeric, oregano and ginger; and therapeutically effectiveamounts of hydroalcoholic extracts of holy basil, ginger, turmeric,Scutellaria baicalensis, rosemary, green tea, huzhang, Chinesegoldthread, and barberry.

In addition, the present inventive subject matter is drawn to a methodfor treating side effects associated with prostate neoplasia in asubject, comprising the step of administering an effective amount of acomposition to said subject to treat said side effects, said compositioncomprising therapeutically effective amounts of supercritical extractsof rosemary, turmeric, oregano and ginger; and therapeutically effectiveamounts of hydroalcoholic extracts of holy basil, ginger, turmeric,Scutellaria baicalensis, rosemary, green tea, huzhang, Chinesegoldthread, and barberry, wherein said side effects are selected fromthe group consisting of disrupted sexual desire or performance on eithera temporary or permanent basis, impotence, extensive monitoring forprogression of the disease, stress of illness, and urinary incontinence.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph which depicts COX-2 inhibition produced by theinventive compositions.

FIG. 2 is a photograph which depicts a Western blot of COX-s expressionin LNCaP cells following treatment with the inventive compositions.

FIG. 3 is a graph which depicts the growth-inhibitory effects of theinventive compositions on LNCaP cells.

FIG. 4 is a photograph which depicts a Western blot of PARP cleavagefragments produced by treatment of LNCaP cells with the inventivecompositions.

FIG. 5 is a graph which depicts Caspase-3 activity in LNCaP cellsfollowing treatment with the inventive compositions.

DETAILED DESCRIPTION OF THE INVENTIVE SUBJECT MATTER Definitions

The term “therapeutically effective amount” as used herein refers tothat amount of the extract which will contribute to the cancer-treatingability of the composition.

The term “treating” as used herein refers to partial or total inhibitionof the growth, spreading, or metastasis of prostate neoplasia, as wellas partial or total destruction of the cancer cells. The term “treating”includes the reduction or elimination of prostate neoplasia, and alsothe reduction in the incidence of the disease.

The term “preventing” as used herein refers to either preventing theonset of prostate neoplasia, or preventing the onset of a preclinicallyevident stage of prostate neoplasia in individuals at risk. Alsointended to be encompassed by this definition is the prevention ofinitiation for malignant cells, and the arrest or reversal of theprogression of premalignant cells to malignant cells. “Preventing” alsoincludes the prevention of growth or spreading of the prostateneoplasia. This includes prophylactic treatment of those at risk ofdeveloping a prostate neoplasia.

The term “supercritical gas” or “supercritical fluid” as used hereinrefers to a gas is that heated to a temperature critical point, overwhich the gas will maintain its gaseous state and not turn to a liquidregardless of pressure. A gas heated to a temperature above its criticalpoint will become very dense on compression, so that its characteristicsresemble those of a fluid, but will become liquid. Carbon dioxide iscommonly used in applications requiring a supercritical fluid. Thegeneral properties of supercritical fluids and the general use ofsupercritical fluids in extraction processes are described in, e.g.Taylor, Supercritical Fluid Extraction, Wiley, 1996; McHugh andKrukonis, Supercritical Fluid Extraction: Principles and Practice, 2nded., Butterworth-Heinemann, 1994; and Williams and Clifford,Supercritical Fluid Methods and Protocols, Humana Press, 2000, thecontents of which are incorporated by reference herein.

The term “supercritical extraction” as used herein refers to thetechnique in which hydrophobic compounds can be extracted from samplesutilizing a supercritical fluid. The salvation power of a supercriticalfluid is increased as the pressure and temperature are increased abovetheir critical points, producing an effective solvent for the isolationof hydrophobic molecules.

The term “hydroalcoholic extraction” as used herein refers to thetechnique in which hydrophillic compounds can be extracted from a sampleutilizing a solution of alcohol and water, followed by evaporation ofthe solution to produce a extract consisting of dissolved solids.

The term “neoplasia” as used herein refers broadly to neoplastic,pre-malignant, and proliferative disease, including specifically benign,premalignant, or malignant neoplasms in individuals with or without anyprior history or diagnosis of neoplastic, pre-malignant, orproliferative disease. The term “neoplasia” includes neoplasia thatproduce prostaglandins or express a cyclooxygenase, including bothbenign and cancerous tumors, growths, and polyps.

The term “prostate neoplasia” as used herein refers broadly toepithelial cancers, epitheliomas, carcinomas, sarcomas, or othermalignant tumors or neoplasia of glandular origin in the prostate.

The term “subject” as used herein refers to any human or mammal subjectwho has a prostate neoplasia, preferably a human subject. For methods ofprevention, the subject is any human or animal subject, preferably ahuman subject, who is at risk for developing an epithelial cell-derivedprostate neoplasia. The subject may be at risk due to exposure tocarcinogenic agents, being genetically predisposed to have a prostateneoplasia, and the like.

The term “cyclooxygenase-2 inhibitor” or “COX-2 inhibitor” as usedherein refers to a compound or composition which is able to inhibitcyclooxygenase-2 without adverse inhibition of cyclooxygenase-1.

Methods for Treating Prostate Cancer

Although the occurrence rate of localized, latent forms of prostatecancer is consistent throughout the world, the occurrence of metastaticprostate cancer is much greater in western countries compared to easterncountries. This striking disparity suggests the involvement ofenvironmental factors in the development of metastatic prostate cancer,and has prompted the initiation of several epidemiological studies whichsuggest a link between high fat diets and risk of metastatic prostatecancer. Both arachidonic acid and its precursor, linoleic acid, arepresent in significant quantities in animal fats and a variety ofvegetable oils. Physiologically, these fatty acids are integralcomponents of cellular membranes and also function as substrates for theproduction of an important group of potent, signaling lipids, termedeicosanoids. Eicosanoids are known to be involved in the initiation ofthe inflammatory response, fever production, regulation of bloodpressure, blood clotting, control of reproductive processes and tissuegrowth, and regulation of the sleep/wake cycle. Additionally, thesepowerful mediators and the enzymes that produce them, cycloxygenases(COX) and lipoxygenases (LO), are implicated in tumor development,progression, and metastasis.

The three main isoforms of cycloxygenase are COX-1, COX-2, and COX-3,and these enzymes are responsible for the production of the group ofeicosanoids, prostaglandins. The COX-1 isoform has many importanthousekeeping functions in the cell, and is therefore constitutivelyproduced throughout the body. COX-2, however, is usually absent untilinduced by specific stimuli. It is therefore not surprising that COX-2is implicated in the progression of many disease states, includingcancer. COX-2 has been found to be present in elevated levels in avariety of cancers, including lung, colon, pancreatic, head and neck,and prostate cancer. As discussed above, COX-3 has only been relativelyrecently identified.

Regarding prostate cancer, it has been demonstrated that elevated levelsof COX-2 are present in some tumor samples, and there is an increasedlevel of COX-2 enzyme expression with disease progression. COX-2activity and resultant prostaglandin production is also involved intumor-induced angiogenesis, which we expect to be mediated by certainCOX-2 inhibitors. Additionally, we expect that certain COX-2 inhibitorsproduce a re-initiation of apoptosis pathways, overcoming theanti-apoptotic factors secreted by cancer cells and leading to celldeath.

The centuries old natural remedy of using white willow bark (Salix alba)to provide some pain relief led to the discovery of aspirin, andeventually, to the elucidation of its mechanism of action as a COXinhibitor. Based on this lead and other traditional Eastern medicinalpractices, many researchers have looked to a variety of natural plantextracts and natural products for the discovery of both non-specific COXand specific COX-2 inhibitors. Some herbal extracts and natural productsthat have peaked interest amongst researchers include curcumin, ginger,holy basil, resveratrol, thundergod vine, and berberine from barberryand Chinese goldthread.

Applicants have developed a mixture comprised of herbal extracts, andthe mixture has COX-2 inhibitory activity. Applicants' compositions areunique, in that they are prepared via a supercritical CO₂ extractionprocess. Unlike traditional solvent based extraction methods,supercritical CO₂ extraction allows the natural products in the herbs tobe obtained without leaving chemical residues behind in the preparation.

Surprisingly, in addition to the anti-inflammatory action disclosed inU.S. Pat. No. 6,387,416, we have found that using the inventivecompositions and methods produce COX-2 inhibition in prostate cancercell lines. We also expect that the inventive methods induce apoptosisand inhibit cell growth in cancer cells which have deactivated apoptoticpathways.

The inventive subject matter is based on the discovery that acombination of certain herbs properly extracted and blended inappropriate proportions can used in treating prostate neoplasia. Thus,the present inventive subject matter relates to a method for treatingprostate neoplasia in a subject, comprising the step of administering aneffective amount of a composition to said subject to treat or preventsaid prostate neoplasia, said composition comprising therapeuticallyeffective amounts of supercritical extracts of rosemary, turmeric,oregano and ginger; and therapeutically effective amounts ofhydroalcoholic extracts of holy basil, ginger, turmeric, Scutellariabaicalensis, rosemary, green tea, huzhang, Chinese goldthread, andbarberry, provided that said prostate neoplasia is not prostaticintraepithelial neoplasia.

In one aspect, said composition is administered orally.

In another preferred embodiment, the orally administered composition isin the form of one or more capsules, one or more tablets, or one or morepills

In another aspect, the composition comprises:

-   -   (A) from about 4.5% to about 7.5%, and more preferably from        about 5.5% to about 6.5%, by weight of the hydroalcoholic        extract of ginger;    -   (B) from about 5.5% to about 8.5%, and more preferably from        about 6% to about 8%, by weight of the supercritical extract of        ginger;    -   (C) from about 1.0% to about 1.5%, and more preferably from        about 1.2% to about 1.4%, by weight of the supercritical extract        of turmeric;    -   (D) from about 10.0% to about 16.0%, and more preferably from        about 11.5% to about 14.5%, by weight of the supercritical        extract of rosemary;    -   (E) from about 4.0% to about 6.0%, and more preferably from        about 4.5% to about 5.5%, by weight of the supercritical extract        of oregano;    -   (F) from about 10.0% to about 16.0%, and more preferably from        about 11.5% to about 14.5%, by weight of the hydroalcoholic        extract of turmeric;    -   (G) from about 5.5% to about 8.0%, and more preferably from        about 6.0% to about 7.0%, by weight of the hydroalcoholic        extract of rosemary;    -   (H) from about 10.0% to about 16.0%, and more preferably from        about 11.5% to about 14.5%, by weight of the hydroalcoholic        extract of holy basil;    -   (I) from about 10.0% to about 16.0%, and more preferably from        about 11.5% to about 14.5%, by weight of the hydroalcoholic        extract of green tea;    -   (J) from about 8.0% to about 12.0%, and more preferably from        about 9.0% to about 11.0%, by weight of the hydroalcoholic        extract of huzhang;    -   (K) from about 4.0% to about 6.0%, and more preferably from        about 4.5% to about 5.5%, by weight of the hydroalcoholic        extract of Chinese goldthread;    -   (L) from about 4.0% to about 6.0%, and more preferably from        about 4.5% to about 5.5%, by weight of the hydroalcoholic        extract of barberry; and    -   (M) from about 2.0% to about 3.0%, and more preferably from        about 2.25% to about 2.75%, by weight of the hydroalcoholic        extract of Scutellaria baicalensis.

The hydroalcoholic extract of ginger used in the present invention ispreferably prepared as follows. The ginger rhizome, which is preferablycryogenically ground to preserve heat sensitive components, is subjectedto supercritical extraction, preferably with carbon dioxide, to obtain:(i) an oil extract, referred to herein as “the supercritical extract” ofginger, containing delicate lipophilic components, and (ii) an oil-freeresidue. The oil-free residue is then extracted in a water/alcohol,preferably water/ethanol, mixture composed of 60-80 parts alcohol and40-20 parts water. The alcohol/water liquid is then evaporated off,leaving a powdered extract residue, referred to herein as “thehydroalcoholic extract” of ginger.

In a preferred aspect, the weight ratio of the supercritical extract ofginger to the hydroalcoholic extract of ginger is from about 0.9:1 toabout 1.4:1.

The supercritical extracts of ginger, rosemary, turmeric and oreganoused in the present invention can be prepared according to knownsupercritical extraction methods, such as disclosed, e.g., in E. Stahl,K. W. Quirin, D. Gerard, Dense Gases for Extraction and Refining,Springer Verlag 4 1988, which is hereby incorporated by referenceherein.

The hydroalcoholic extracts of rosemary, turmeric, holy basil, greentea, huzhang, Chinese goldthread, barberry and Scutellaria baicalensisused in the present invention can be prepared according to conventionalhydroalcoholic extraction techniques. For example, the hydroalcoholicextracts can be prepared by extracting the plant portion in awater/alcohol, preferably water/ethanol, mixture preferably composed of60-80 parts alcohol and 40-20 parts water, and then evaporating off thewater/alcohol liquid, leaving a powdered extract residue referred toherein as “the hydroalcoholic extract”.

In yet another aspect, the weight ratio of the hydroalcoholic extract ofturmeric to the supercritical extract of turmeric is from about 8:1 toabout 12:1.

In an alternate aspect, the weight ratio of the supercritical extract ofrosemary to the hydroalcoholic extract of rosemary is from about 1.6:1to about 2.4:1.

In a still further aspect, the hydroalcoholic extract of gingercomprises from about 2.4% to about 3.6%, more preferably from about 2.7%to about 3.3%, and most preferably about 3.0%, by weight of pungentcompounds.

In another aspect, the supercritical extract of ginger comprises fromabout 24% to about 36%, more preferably from about 27% to about 33%, andmost preferably about 30%, by weight of pungent compounds; and fromabout 6.4% to about 9.6%, more preferably from about 7.2% to about 8.8%,and most preferably about 8%, by weight of zingiberene.

In a further aspect, the supercritical extract of turmeric comprisesfrom about 36% to about 54%, more preferably from about 40.5% to about49.5%, and most preferably about 45%, by weight of turmerones.

In another aspect, the supercritical extract of rosemary comprises fromabout 18.4% to about 27.6%, more preferably from about 20.7% to about25.3%, and most preferably about 23%, by weight of total phenolicantioxidants.

In yet another aspect, the supercritical extract of oregano comprisesfrom about 0.64% to about 0.96%, more preferably from about 0.72% toabout 0.88%, and most preferably about 0.8%, by weight of total phenolicantioxidants.

In a still further aspect, the hydroalcoholic extract of turmericcomprises from about 5.6% to about 8.4%, more preferably from about 6.3%to about 7.7%, and most preferably about 7%, by weight of curcumin.

In another aspect, the hydroalcoholic extract of rosemary comprises fromabout 18.4% to about 27.6%, more preferably from about 20.7% to about25.3%, and most preferably about 23%, by weight of total phenolicantioxidants.

In a further embodiment, the hydroalcoholic extract of holy basilcomprises from about 1.6% to about 2.4%, more preferably from about 1.8%to about 2.2%, and most preferably about 2%, by weight of ursolic acid.

In a further aspect, the hydroalcoholic extract of green tea comprisesfrom about 36% to about 54%, more preferably from about 40.5% to about49.5%, and most preferably about 45%, by weight of polyphenols.

In another aspect, the hydroalcoholic extract of huzhang comprises fromabout 6.4% to about 9.6%, more preferably from about 7.2% to about 8.8%,and most preferably about 8%, by weight of resveratrol.

In another embodiment, the hydroalcoholic extract of Chinese goldthreadcomprises from about 4.8% to about 7.2%, more preferably from about 5.4%to about 6.6%, and most preferably about 6%, by weight of berberine.

In a further aspect, the hydroalcoholic extract of barberry comprisesfrom about 4.8% to about 7.2%, more preferably from about 5.4% to about6.6%, and most preferably about 6%, by weight of berberine.

In an alternate aspect, said composition comprises:

-   -   (A) from about 4.5% to about 7.5% by weight of the        hydroalcoholic extract of ginger, wherein the extract comprises        from about 2.4% to about 3.6% by weight of pungent compounds;    -   (B) from about 5.5% to about 8.5% by weight of the supercritical        extract of ginger, wherein the extract comprises from about 24%        to about 36% by weight of pungent compounds and from about 6.4%        to about 9.6% by weight of zingiberene;    -   (C) from about 1.0% to about 1.5% by weight of the supercritical        extract of turmeric, wherein the extract comprises from about        36% to about 54% by weight of turmerones;    -   (D) from about 10.0% to about 16.0% by weight of the        supercritical extract of rosemary, wherein the extract comprises        from about 18.4% to about 27.6% by weight of total phenolic        antioxidants;    -   (E) from about 4.0% to about 6.0% by weight of the supercritical        extract of oregano, wherein the extract comprises from about        0.64% to about 0.96% by weight of total phenolic antioxidants;    -   (F) from about 10.0% to about 16.0% by weight of the        hydroalcoholic extract of turmeric, wherein the extract        comprises from about 5.6% to about 8.4% by weight of curcumin;    -   (G) from about 5.5% to about 8.0% by weight of the        hydroalcoholic extract of rosemary, wherein the extract        comprises from about 18.4% to about 27.6% by weight of total        phenolic antioxidants;    -   (H) from about 10.0% to about 16.0% by weight of the        hydroalcoholic extract of holy basil, wherein the extract        comprises from about 1.6% to about 2.4% by weight of ursolic        acid;    -   (I) from about 10.0% to about 16.0% by weight of the        hydroalcoholic extract of green tea, wherein the extract        comprises from about 36% to about 54% by weight of polyphenols;    -   (J) from about 8.0% to about 12.0% by weight of the        hydroalcoholic extract of huzhang, wherein the extract comprises        from about 6.4% to about 9.6% by weight of resveratrol;    -   (K) from about 4.0% to about 6.0% by weight of the        hydroalcoholic extract of Chinese goldthread, wherein the        extract from about 4.8% to about 7.2% by weight of berberine;    -   (L) from about 4.0% to about 6.0% by weight of the        hydroalcoholic extract of barberry, wherein the extract from        about 4.8% to about 7.2% by weight of berberine; and    -   (M) from about 2.0% to about 3.0% by weight of the        hydroalcoholic extract of Scutellaria baicalensis; and wherein        said composition further comprises:    -   (i) the supercritical extract of ginger and the        post-supercritical hydroalcoholic extract of ginger at a weight        ratio of from about 0.9 to about 1.4 parts of supercritical        extract per 1 part of post-supercritical hydroalcoholic extract;    -   (ii) the hydroalcoholic extract of turmeric and the        supercritical extract of turmeric at a weight ratio of from        about 8 to about 12 parts of hydroalcoholic extract per 1 part        of supercritical extract; and    -   (iii) the supercritical extract of rosemary and the        hydroalcoholic extract of rosemary at a weight ratio of from        about 1.6 to about 2.4 parts of supercritical extract per 1 part        of hydroalcoholic extract.

In a preferred embodiment, the composition is administered in a dailydosage of at least about 700 mg.

In another aspect, the composition is administered on a daily basis forat least 4 weeks.

A still further aspect of the present inventive subject matter is drawnto a method for treating at least one cancerous tumor of the prostate ina subject, comprising the step of administering an effective amount of acomposition to said subject to treat said tumor, said compositioncomprising therapeutically effective amounts of supercritical extractsof rosemary, turmeric, oregano and ginger; and therapeutically effectiveamounts of hydroalcoholic extracts of holy basil, ginger, turmeric,Scutellaria baicalensis, rosemary, green tea, huzhang, Chinesegoldthread, and barberry.

In a still further embodiment of the present inventive subject matter,the at least one cancerous tumor is detected during surgery on theprostate of said subject, having not been felt by a physician onphysical examination of said subject.

Yet still further, the present inventive subject matter includes the atleast one cancerous tumor being confined to the prostate of said subjectand is detected by a physician on physical examination of said subject.

An additional aspect of the present invention includes the cancerrelated to said at least one cancerous tumor extends beyond the prostatecapsule of said subject, but has not spread to lymph nodes in saidsubject.

A further additional aspect of the present inventive subject matter isdirected to the cancer related to said at least one cancerous tumor ismetastasized to regional lymph nodes or other parts of said subject.

A preferred aspect of the present invention is directed to a method fortreating side effects associated with prostate neoplasia in a subject,comprising the step of administering an effective amount of acomposition to said subject to treat said side effects, said compositioncomprising therapeutically effective amounts of supercritical extractsof rosemary, turmeric, oregano and ginger; and therapeutically effectiveamounts of hydroalcoholic extracts of holy basil, ginger, turmeric,Scutellaria baicalensis, rosemary, green tea, huzhang, Chinesegoldthread, and barberry,

wherein said side effects are selected from the group consisting ofdisrupted sexual desire or performance on either a temporary orpermanent basis, impotence, extensive monitoring for progression of thedisease, stress of illness, and urinary incontinence.

A further preferred embodiment is drawn to the method wherein the sideeffect treated comprises disrupted sexual performance.

In an alternate aspect, the composition comprises an additional agentselected from the group consisting of antineoplastic agents, growthinhibiting agents, and nutrients.

There are large numbers of antineoplastic agents available in commercialuse, in clinical evaluation and in pre-clinical development, whichoptionally are selected for treatment of prostate neoplasia bycombination drug chemotherapy. Such antineoplastic agents fall intoseveral major categories: antimetabolite agents, antibiotic-type agents,alkylating agents, hormonal agents, immunological agents,interferon-type agents, metallomatrix proteases, superoxide dismutasemimics or α_(v)β₃ inhibitors. Thus, in a preferred embodiment, saidantineoplastic agent is selected from the group consisting ofantimetabolite agents, antibiotic-type agents, alkylating agents,hormonal agents, immunological agents, interferon-type agents,metallomatrix proteases, superoxide dismutase mimics, and α_(v)β₃inhibitors.

One class of antineoplastic agents which may be used in combination withan inventive composition consists of antimetabolite-type antineoplasticagents. Suitable antimetabolite antineoplastic agents may be selectedfrom the group consisting of 5-FU-fibrinogen, acanthifolic acid,aminothiadiazole, brequinar sodium, carmofur, Ciba-Geigy CGP-30694,cyclopentyl cytosine, cytarabine phosphate stearate, cytarabineconjugates, Lilly DATHF, Merrel Dow DDFC, dezaguanine, dideoxycytidine,dideoxyguanosine, didox, Yoshitomi DMDC, doxifluridine, Wellcome EHNA,Merck & Co. EX-015, fazarabine, floxuridine, fludarabine phosphate,5-fluorouracil, N-(2′-furanidyl)-5-fluorouracil, Daiichi Seiyaku FO-152,isopropyl pyrrolizine, Lilly LY-188011, Lilly LY-264618, methobenzaprim,methotrexate, Wellcome MZPES, norspermidine, NCI NSC-127716, NCINSC-264880, NCI NSC-39661, NCI NSC-612567, Warner-Lambert PALA,pentostatin, piritrexim, plicamycin, Asahi Chemical PL-AC, TakedaTAC-788, thioguanine, tiazofurin, Erbamont TIF, trimetrexate, tyrosinekinase inhibitors, tyrosine protein kinase inhibitors, Taiho UFT, anduricytin.

A second class of antineoplastic agents which may be used in combinationwith an inventive composition consists of alkylating-type antineoplasticagents. Suitable alkylating-type antineoplastic agents may be selectedfrom the group consisting of Shionogi 254-S, aldo-phosphamide analogues,altretamine, anaxirone, Boehringer Mannheim BBR-2207, bestrabucil,budotitane, Wakunaga CA-102, carboplatin, carmustine, Chinoin-139,Chinoin-153, chlorambucil, cisplatin, cyclophosphamide, AmericanCyanamid CL-286558, Sanofi CY-233, cyplatate, Degussa D-19-384, SumimotoDACHP(Myr)₂, diphenylspiromustine, diplatinum cytostatic, Erbadistamycin derivatives, Chugai DWA-2114R, ITI E09, elmustine, ErbamontFCE-24517, estramustine phosphate sodium, fotemustine, Unimed G-6-M,Chinoin GYKI-17230, hepsul-fam, ifosfamide, iproplatin, lomustine,mafosfamide, mitolactol, Nippon Kayaku NK-121, NCI NSC-264395, NCINSC-342215, oxaliplatin, Upjohn PCNU, prednimustine, Proter PTT-119,ranimustine, semustine, SmithKline SK&F-101772, Yakult Honsha SN-22,spiromustine, Tanabe Seiyaku TA-077, tauromustine, temozolomide,teroxirone, tetraplatin, and trimelamol.

A third class of antineoplastic agents which may be used in combinationwith an inventive composition consists of antibiotic-type antineoplasticagents. Suitable antibiotic-type antineoplastic agents may be selectedfrom the group consisting of Taiho 4181-A, aclarubicin, actinomycin D,actinoplanone, Erbamont ADR-456, aeroplysinin derivative, AjinomotoAN-201-II, Ajinomoto AN-3, Nippon Soda anisomycins, anthracycline,azino-mycin-A, bisucaberin, Bristol-Myers BL-6859, Bristol-MyersBMY-25067, Bristol-Myers BMY-25551, Bristol-Myers BMY-26605,Bristol-Myers BMY-27557, Bristol-Myers BMY-28438, bleomycin sulfate,bryostatin-1, Taiho C-1027, calichemycin, chromoximycin, dactinomycin,daunorubicin, Kyowa Hakko DC-102, Kyowa Hakko DC-79, Kyowa Hakko DC-88A,Kyowa Hakko DC89-A1, Kyowa Hakko DC92-B, ditrisarubicin B, ShionogiDOB-41, doxorubicin, doxorubicin-fibrinogen, elsamicin-A, epirubicin,erbstatin, esorubicin, esperamicin-A1, esperamicin-Alb, ErbamontFCE-21954, Fujisawa FK-973, fostriecin, Fujisawa FR-900482, glidobactin,gregatin-A, grincamycin, herbimycin, idarubicin, illudins, kazusamycin,kesarirhodins, Kyowa Hakko KM-5539, Kirin Brewery KRN-8602, Kyowa HakkoKT-5432, Kyowa Hakko KT-5594, Kyowa Hakko KT-6149, American CyanamidLL-D49194, Meiji Seika ME 2303, menogaril, mitomycin, mitoxantrone,SmithKline M-TAG, neoenactin, Nippon Kayaku NK-313, Nippon KayakuNKT-01, SRI International NSC-357704, oxalysine, oxaunomycin,peplomycin, pilatin, pirarubicin, porothramycin, pyrindamycin A, TobishiRA-I, rapamycin, rhizoxin, rodorubicin, sibanomicin, siwenmycin,Sumitomo SM-5887, Snow Brand SN-706, Snow Brand SN-07, sorangicin-A,sparsomycin, SS Pharmaceutical SS-21020, SS Pharmaceutical SS-7313B, SSPharmaceutical SS-9816B, steffimycin B, Taiho 4181-2, talisomycin,Takeda TAN-868A, terpentecin, thrazine, tricrozarin A, Upjohn U-73975,Kyowa Hakko UCN-10028A, Fujisawa WF-3405, Yoshitomi Y-25024, andzorubicin.

A fourth class of antineoplastic agents which may be used in combinationwith an inventive composition consists of a miscellaneous family ofantineoplastic agents selected from the group consisting ofalpha-carotene, alpha-difluoromethyl-arginine, acitretin, Biotec AD-5,Kyorin AHC-52, alstonine, amonafide, amphethinile, amsacrine, Angiostat,ankinomycin, anti-neoplaston A10, antineoplaston A2, antineoplaston A3,antineoplaston A5, antineoplaston AS2-1, Henkel APD, aphidicolinglycinate, asparaginase, Avarol, baccharin, batracylin, benfluoron,benzotript, Ipsen-Beaufour BIM-23015, bisantrene, Bristo-MyersBMY-40481, Vestar boron-10, bromofosfamide, Wellcome BW-502, WellcomeBW-773, caracemide, carmethizole hydrochloride, Ajinomoto CDAF,chlorsulfaquinoxalone, Chemes CHX-2053, Chemex CHX-100, Warner-LambertCI-921, Warner-Lambert CI-937, Warner-Lambert CI-941, Warner-LambertCI-958, clanfenur, claviridenone, ICN compound 1259, ICN compound 4711,Contracan, Yakult Honsha CPT-11, crisnatol, curaderm, cytochalasin B,cytarabine, cytocytin, Merz D-609, DABIS maleate, dacarbazine,datelliptinium, didemnin-B, dihaematoporphyrin ether, dihydrolenperone,dinaline, distamycin, Toyo Pharmar DM-341, Toyo Pharmar DM-75, DaiichiSeiyaku DN-9693, elliprabin, elliptinium acetate, Tsumura EPMTC,ergotamine, etoposide, etretinate, fenretinide, Fujisawa FR-57704,gallium nitrate, genkwadaphnin, Chugai GLA-43, Glaxo GR-63178, grifolanNMF-5N, hexadecylphosphocholine, Green Cross HO-221, homoharringtonine,hydroxyurea, BTG ICRF-187, ilmofosine, isoglutamine, isotretinoin,Otsuka JI-36, Ramot K-477, Otsuak K-76COONa, Kureha Chemical K-AM, MECTCorp KI-8110, American Cyanamid L-623, leukoregulin, lonidamine,Lundbeck LU-23-112, Lilly LY-186641, NCl (US) MAP, marycin, Merrel DowMDL-27048, Medco MEDR-340, merbarone, merocyanine derivatives,methylanilinoacridine, Molecular Genetics MGI-136, minactivin,mitonafide, mitoquidone, mopidamol, motretinide, Zenyaku Kogyo MST-16,N-(retinoyl)amino acids, Nisshin Flour Milling N-021,N-acylated-dehydroalanines, nafazatrom, Taisho NCU-190, nocodazolederivative, Normosang, NCI NSC-145813, NCI NSC-361456, NCI NSC-604782,NCI NSC-95580, octreotide, Ono ONO-112, oquizanocine, Akzo Org-10172,pancratistatin, pazelliptine, Warner-Lambert PD-111707, Warner-LambertPD-115934, Warner-Lambert PD-131141, Pierre Fabre PE-1001, ICRT peptideD, piroxantrone, polyhaematoporphyrin, polypreic acid, Efamol porphyrin,probimane, procarbazine, proglumide, Invitron protease nexin I, TobishiRA-700, razoxane, Sapporo Breweries RBS, restrictin-P, retelliptine,retinoic acid, Rhone-Poulenc RP-49532, Rhone-Poulenc RP-56976,SmithKline SK&F-104864, Sumitomo SM-108, Kuraray SMANCS, SeaPharmSP-10094, spatol, spirocyclopropane derivatives, spirogermanium, Unimed,SS Pharmaceutical SS-554, strypoldinone, Stypoldione, Suntory SUN 0237,Suntory SUN 2071, superoxide dismutase, Toyama T-506, Toyama T-680,taxol, Teijin TEI-0303, teniposide, thaliblastine, Eastman Kodak TJB-29,tocotrienol, Topostin, Teijin TT-82, Kyowa Hakko UCN-01, Kyowa HakkoUCN-1028, ukrain, Eastman Kodak USB-006, vinblastine sulfate,vincristine, vindesine, vinestramide, vinorelbine, vintriptol,vinzolidine, withanolides, and Yamanouchi YM-534.

Examples of radioprotective agents which may be used in the combinationchemotherapy of this invention are AD-5, adchnon, amifostine analogues,detox, dimesna, 1-102, MM-159, N-acylated-dehydroalanines,TGF-Genentech, tiprotimod, amifostine, WR-151327, FUT-187, ketoprofentransdermal, nabumetone, superoxide dismutase (Chiron), and superoxidedismutase Enzon.

Thus, in a further preferred embodiment, said antineoplastic agent isselected from the group consisting of 5-FU-fibrinogen, acanthifolicacid, aminothiadiazole, brequinar sodium, carmofur, Ciba-GeigyCGP-30694, cyclopentyl cytosine, cytarabine phosphate stearate,cytarabine conjugates, Lilly DATHF, Merrel Dow DDFC, dezaguanine,dideoxycytidine, dideoxyguanosine, didox, Yoshitomi DMDC, doxifluridine,Wellcome EHNA, Merck & Co. EX-015, fazarabine, floxuridine, fludarabinephosphate, 5-fluorouracil, N-(2′-furanidyl)-5-fluorouracil, DaiichiSeiyaku FO-152, isopropyl pyrrolizine, Lilly LY-188011, Lilly LY-264618,methobenzaprim, methotrexate, Wellcome MZPES, norspermidine, NCINSC-127716, NCI NSC-264880, NCI NSC-39661, NCI NSC-612567,Warner-Lambert PALA, pentostatin, piritrexim, plicamycin, Asahi ChemicalPL-AC, Takeda TAC-788, thioguanine, tiazofurin, Erbamont TIF,trimetrexate, tyrosine kinase inhibitors, tyrosine protein kinaseinhibitors, Taiho UFT, uricytin, Shionogi 254-S, aldo-phosphamideanalogues, altretamine, anaxirone, Boehringer Mannheim BBR-2207,bestrabucil, budotitane, Wakunaga CA-102, carboplatin, carmustine,Chinoin-139, Chinoin-153, chlorambucil, cisplatin, cyclophosphamide,American Cyanamid CL-286558, Sanofi CY-233, cyplatate, Degussa D-19-384,Sumimoto DACHP(Myr)₂, diphenylspiromustine, diplatinum cytostatic, Erbadistamycin derivatives, Chugai DWA-2114R, ITI E09, elmustine, ErbamontFCE-24517, estramustine phosphate sodium, fotemustine, Unimed G-6-M,Chinoin GYKI-17230, hepsul-fam, ifosfamide, iproplatin, lomustine,mafosfamide, mitolactol, Nippon Kayaku NK-121, NCI NSC-264395, NCINSC-342215, oxaliplatin, Upjohn PCNU, prednimustine, Proter PTT-119,ranimustine, semustine, SmithKline SK&F-101772, Yakult Honsha SN-22,spiromustine, Tanabe Seiyaku TA-077, tauromustine, temozolomide,teroxirone, tetraplatin, trimelamol, Taiho 4181-A, aclarubicin,actinomycin D, actinoplanone, Erbamont ADR-456, aeroplysinin derivative,Ajinomoto AN-201-II, Ajinomoto AN-3, Nippon Soda anisomycins,anthracycline, azino-mycin-A, bisucaberin, Bristol-Myers BL-6859,Bristol-Myers BMY-25067, Bristol-Myers BMY-25551, Bristol-MyersBMY-26605, Bristol-Myers BMY-27557, Bristol-Myers BMY-28438, bleomycinsulfate, bryostatin-1, Taiho C-1027, calichemycin, chromoximycin,dactinomycin, daunorubicin, Kyowa Hakko DC-102, Kyowa Hakko DC-79, KyowaHakko DC-88A, Kyowa Hakko DC89-A1, Kyowa Hakko DC92-B, ditrisarubicin B,Shionogi DOB-41, doxorubicin, doxorubicin-fibrinogen, elsamicin-A,epirubicin, erbstatin, esorubicin, esperamicin-A1, esperamicin-Alb,Erbamont FCE-21954, Fujisawa FK-973, fostriecin, Fujisawa FR-900482,glidobactin, gregatin-A, grincamycin, herbimycin, idarubicin, illudins,kazusamycin, kesarirhodins, Kyowa Hakko KM-5539, Kirin Brewery KRN-8602,Kyowa Hakko KT-5432, Kyowa Hakko KT-5594, Kyowa Hakko KT-6149, AmericanCyanamid LL-D49194, Meiji Seika ME 2303, menogaril, mitomycin,mitoxantrone, SmithKline M-TAG, neoenactin, Nippon Kayaku NK-313, NipponKayaku NKT-01, SRI International NSC-357704, oxalysine, oxaunomycin,peplomycin, pilatin, pirarubicin, porothramycin, pyrindamycin A, TobishiRA-I, rapamycin, rhizoxin, rodorubicin, sibanomicin, siwenmycin,Sumitomo SM-5887, Snow Brand SN-706, Snow Brand SN-07, sorangicin-A,sparsomycin, SS Pharmaceutical SS-21020, SS Pharmaceutical SS-7313B, SSPharmaceutical SS-9816B, steffimycin B, Taiho 4181-2, talisomycin,Takeda TAN-868A, terpentecin, thrazine, tricrozarin A, Upjohn U-73975,Kyowa Hakko UCN-10028A, Fujisawa WF-3405, Yoshitomi Y-25024, zorubicin,alpha-carotene, alpha-difluoromethyl-arginine, acitretin, Biotec AD-5,Kyorin AHC-52, alstonine, amonafide, amphethinile, amsacrine, Angiostat,ankinomycin, anti-neoplaston A10, antineoplaston A2, antineoplaston A3,antineoplaston A5, antineoplaston AS2-1, Henkel APD, aphidicolinglycinate, asparaginase, Avarol, baccharin, batracylin, benfluoron,benzotript, Ipsen-Beaufour BIM-23015, bisantrene, Bristo-MyersBMY-40481, Vestar boron-10, bromofosfamide, Wellcome BW-502, WellcomeBW-773, caracemide, carmethizole hydrochloride, Ajinomoto CDAF,chlorsulfaquinoxalone, Chemes CHX-2053, Chemex CHX-100, Warner-LambertCI-921, Warner-Lambert CI-937, Warner-Lambert CI-941, Warner-LambertCI-958, clanfenur, claviridenone, ICN compound 1259, ICN compound 4711,Contracan, Yakult Honsha CPT-11, crisnatol, curaderm, cytochalasin B,cytarabine, cytocytin, Merz D-609, DABIS maleate, dacarbazine,datelliptinium, didemnin-B, dihaematoporphyrin ether, dihydrolenperone,dinaline, distamycin, Toyo Pharmar DM-341, Toyo Pharmar DM-75, DaiichiSeiyaku DN-9693, elliprabin, elliptinium acetate, Tsumura EPMTC,ergotamine, etoposide, etretinate, fenretinide, Fujisawa FR-57704,gallium nitrate, genkwadaphnin, Chugai GLA-43, Glaxo GR-63178, grifolanNMF-5N, hexadecylphosphocholine, Green Cross HO-221, homoharringtonine,hydroxyurea, BTG ICRF-187, ilmofosine, isoglutamine, isotretinoin,Otsuka JI-36, Ramot K-477, Otsuak K-76COONa, Kureha Chemical K-AM, MECTCorp KI-8110, American Cyanamid L-623, leukoregulin, lonidamine,Lundbeck LU-23-112, Lilly LY-186641, NCl (US) MAP, marycin, Merrel DowMDL-27048, Medco MEDR-340, merbarone, merocyanine derivatives,methylanilinoacridine, Molecular Genetics MGI-136, minactivin,mitonafide, mitoquidone, mopidamol, motretinide, Zenyaku Kogyo MST-16,N-(retinoyl)amino acids, Nisshin Flour Milling N-021,N-acylated-dehydroalanines, nafazatrom, Taisho NCU-190, nocodazolederivative, Normosang, NCI NSC-145813, NCI NSC-361456, NCI NSC-604782,NCI NSC-95580, octreotide, Ono ONO-112, oquizanocine, Akzo Org-10172,pancratistatin, pazelliptine, Warner-Lambert PD-111707, Warner-LambertPD-115934, Warner-Lambert PD-131141, Pierre Fabre PE-1001, ICRT peptideD, piroxantrone, polyhaematoporphyrin, polypreic acid, Efamol porphyrin,probimane, procarbazine, proglumide, Invitron protease nexin I, TobishiRA-700, razoxane, Sapporo Breweries RBS, restrictin-P, retelliptine,retinoic acid, Rhone-Poulenc RP-49532, Rhone-Poulenc RP-56976,SmithKline SK&F-104864, Sumitomo SM-108, Kuraray SMANCS, SeaPharmSP-10094, spatol, spirocyclopropane derivatives, spirogermanium, Unimed,SS Pharmaceutical SS-554, strypoldinone, Stypoldione, Suntory SUN 0237,Suntory SUN 2071, superoxide dismutase, Toyama T-506, Toyama T-680,taxol, Teijin TEI-0303, teniposide, thaliblastine, Eastman Kodak TJB-29,tocotrienol, Topostin, Teijin TT-82, Kyowa Hakko UCN-01, Kyowa HakkoUCN-1028, ukrain, Eastman Kodak USB-006, vinblastine sulfate,vincristine, vindesine, vinestramide, vinorelbine, vintriptol,vinzolidine, withanolides, Yamanouchi YM-534, AD-5, adchnon, amifostineanalogues, detox, dimesna, 1-102, MM-159, N-acylated-dehydroalanines,TGF-Genentech, tiprotimod, amifostine, WR-151327, FUT-187, ketoprofentransdermal, nabumetone, and superoxide dismutase.

A benefit provided by the inventive compositions is the utilization ofsupercritical extraction, an innovative technology for extracting herbsat low temperature without the use of industrial chemical solvents. Suchextraction process allows for the highest potency of active compounds inthe extracts, as much as 250 times the potency of the original freshplant material.

Set forth in Table I is a preferred embodiment of the orallyadministered composition, excluding inactive ingredients, as used in theinventive methods. The amounts recited in Table I represent thepreferred dosage of the ingredients listed.

TABLE I Plant Amount Herb Type Of Extract Part (mg) Rosemarysupercritical leaf 100 Rosemary hydroalcoholic (23% TPA - 34.5 mg) leaf50 Turmeric supercritical (45% turmerones - 4.5 mg) rhizome 10 Turmerichydroalcoholic (7% curcumin - 7 mg) rhizome 100 Ginger supercritical(30% pungent compounds - rhizome 54 16.2 mg 8% zingiberene - 4.3 mg)Ginger hydroalcoholic (3% pungent rhizome 46 compounds - 1.4 mg) Holybasil hydroalcoholic (2% ursolic acid - 2 mg) leaf 100 Green teahydroalcoholic (45% polyphenols - leaf 100 45 mg) Huzhang hydroalcoholic(8% resveratrol - root & 80 6.4 mg) rhizome Chinese hydroalcoholic (6%berberine - 2.4 mg) root 40 Goldthread Barberry hydroalcoholic (6%berberine - 2.4 mg) root 40 Oregano supercritical (0.8% TPA - 0.32 mg)leaf 40 Scutellaria hydroalcoholic (5:1) root 20 Baicalensis

Preferably, the composition set forth in Table I also includes extravirgin olive oil and yellow beeswax.

The inventive methods use a therapeutically effective amount of theactive compositions indicated above. This effective amount willgenerally comprise from about 0.1 mg to about 100 mg of the active agentper kilogram of patient body weight per day. This effective amount canvary depending upon the physical status of the patient and other factorswell known in the art. Moreover, it will be understood that this dosageof active agent can be administered in a single or multiple dosage unitsto provide the desired therapeutic effect. If desired, other therapeuticagents can be employed in conjunction with those provided by the presentinventive subject matter.

The inventive methods use compositions which are preferably delivered tothe patient by means of a pharmaceutically acceptable carrier. Suchcarriers are well known in the art and generally will be in either solidor liquid form. Solid form pharmaceutical preparations which may beprepared according to the present inventive subject matter includepowders, tablets, dispersible granules, capsules, and cachets. Ingeneral, solid form preparations will comprise from about 5% to about90% by weight of the active agent.

A solid carrier can be one or more substances which may also act asdiluents, flavoring agents, solubilizers, lubricants, suspending agents,binders or tablet disintegrating agents; it can also be encapsulatingmaterial. In powders, the carrier is a finely divided solid which is inadmixture with the viscous active compound. In tablets, the activecompound is mixed with a carrier having the necessary binding propertiesin suitable proportions and compacted to the shape and size desired.Suitable solid carriers include magnesium carbonate, magnesium stearate,talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth,methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoabutter, and the like. The term “preparation” is intended to include theformulation of the active compound with encapsulating materials as acarrier which may provide a capsule in which the active component (withor without other carriers) is surrounded by carrier, which is thus inassociation with it. Similarly, cachets are included. Tablets, powders,cachets, and capsules can be used as solid dosage forms suitable fororal administration. If desired for reasons of convenience or patientacceptance, pharmaceutical tablets prepared according to the inventivesubject matter may be provided in chewable form, using techniques wellknown in the art.

Also contemplated as suitable carriers are solid form preparations whichare intended to be converted, shortly before use, to liquid formpreparations for either oral or parenteral administration. Such liquidforms include solutions, suspensions, and emulsions. These particularsolid form preparations are most conveniently provided in unit dose formand as such are used to provide a single liquid dosage unit.Alternately, sufficient solid may be provided so that after conversionto liquid form, multiple individual liquid doses may be obtained bymeasuring predetermined volumes of the liquid form preparation as with asyringe, teaspoon, or other volumetric container. When multiple liquiddoses are so prepared, it is preferred to maintain the unused portion ofsaid liquid doses at low temperature (i.e., under refrigeration) inorder to retard possible decomposition. The solid form preparationsintended to be converted to liquid form may contain, in addition to theactive material, flavorants, colorants, stabilizers, buffers, artificialand natural sweeteners, dispersants, thickeners, solubilizing agents,and the like. The liquid utilized for preparing useful liquid formpreparations may be water, isotonic water, ethanol, glycerine, propyleneglycol, and the like as well as mixtures thereof. Naturally, the liquidutilized will be chosen with regard to the route of administration. Forexample, liquid preparations containing large amounts of ethanol are notsuitable for parenteral use.

The pharmaceutical preparation may also be in a unit dosage form. Insuch form, the preparation is subdivided into unit doses containingappropriate quantities of the active component. The unit dosage form canbe a packaged preparation, the package containing discrete quantities ofpreparation, for example, packeted tablets, capsules, and powders invials or ampoules. The unit dosage form can also be a capsule, cachet,or tablet itself or it can be the appropriate number of any of these inpackaged form.

The pharmaceutical preparations of the inventive subject matter mayinclude one or more preservatives well known in the art, such as benzoicacid, sorbic acid, methylparaben, propylparaben andethylenediaminetetraacetic acid (EDTA). Preservatives are generallypresent in amounts up to about 1% and preferably from about 0.05 toabout 0.5% by weight of the pharmaceutical composition.

Useful buffers for purposes of the inventive subject matter includecitric acid-sodium citrate, phosphoric acid-sodium phosphate, and aceticacid-sodium acetate in amounts up to about 1% and preferably from about0.05 to about 0.5% by weight of the pharmaceutical composition. Usefulsuspending agents or thickeners include cellulosics likemethylcellulose, carageenans like alginic acid and its derivatives,xanthan gums, gelatin, acacia, and microcrystalline cellulose in amountsup to about 20% and preferably from about 1% to about 15% by weight ofthe pharmaceutical composition.

Sweeteners which may be employed include those sweeteners, both naturaland artificial, well known in the art. Sweetening agents such asmonosaccharides, disaccharides and polysaccharides such as xylose,ribose, glucose, mannose, galactose, fructose, dextrose, sucrose,maltose, partially hydrolyzed starch or corn syrup solids and sugaralcohols such as sorbitol, xylitol, mannitol and mixtures thereof may beutilized in amounts from about 10% to about 60% and preferably fromabout 20% to about 50% by weight of the pharmaceutical composition.Water soluble artificial sweeteners such as saccharin and saccharinsalts such as sodium or calcium, cyclamate salts, acesulfame-K,aspartame and the like and mixtures thereof may be utilized in amountsfrom about 0.001% to about 5% by weight of the composition.

Flavorants which may be employed in the pharmaceutical products of theinventive subject matter include both natural and artificial flavors,and mints such as peppermint, menthol, vanilla, artificial vanilla,chocolate, artificial chocolate, cinnamon, various fruit flavors, bothindividually and mixed, in amounts from about 0.5% to about 5% by weightof the pharmaceutical composition.

Colorants useful in the present inventive subject matter includepigments which may be incorporated in amounts of up to about 6% byweight of the composition. A preferred pigment, titanium dioxide, may beincorporated in amounts up to about 1%. Also, the colorants may includeother dyes suitable for food, drug and cosmetic applications, known asF.D.&C. dyes and the like. Such dyes are generally present in amounts upto about 0.25% and preferably from about 0.05% to about 0.2% by weightof the pharmaceutical composition. A full recitation of all F.D.&C. andD.&C. dyes and their corresponding chemical structures may be found inthe Kirk-Othmer Encyclopedia of Chemical Technology, in Volume 5, atpages 857-884, which text is accordingly incorporated herein byreference.

Useful solubilizers include alcohol, propylene glycol, polyethyleneglycol and the like and may be used to solubilize the flavors.Solubilizing agents are generally present in amounts up to about 10%;preferably from about 2% to about 5% by weight of the pharmaceuticalcomposition.

Lubricating agents which may be used when desired in the instantcompositions include silicone oils or fluids such as substituted andunsubstituted polysiloxanes, e.g., dimethyl polysiloxane, also known asdimethicone. Other well known lubricating agents may be employed.

It is not expected that the inventive methods use compositions whichwill display significant adverse interactions with other synthetic ornaturally occurring substances. Thus, a compound of the presentinventive subject matter may be administered in combination with othercompounds and compositions useful for treating prostate neoplasia. Inparticular the inventive methods use compositions which may beadministered in combination with other inventive compositions, otherantineoplastic substances, and the like.

The optimal pharmaceutical formulations will be determined by oneskilled in the art depending upon considerations such as the route ofadministration and desired dosage. See, for example, “Remington'sPharmaceutical Sciences”, 18th ed. (1990, Mack Publishing Co., Easton,Pa. 18042), pp. 1435-1712, which is hereby incorporated by reference inits entirety. Such formulations may influence the physical state,stability, rate of in vivo release, and rate of in vivo clearance of thepresent therapeutic agents of the inventive subject matter.

Route(s) of Administration

The compounds and compositions are preferably administered orally in theform of capsules, tablets, aqueous suspensions, or solutions. Tabletsmay contain carriers such as lactose and corn starch, and/or lubricatingagents such as magnesium stearate. Capsules may contain diluentsincluding lactose and dried corn starch. Aqueous suspensions may containemulsifying and suspending agents combined with the active ingredient.The oral dosage forms may further contain sweetening, flavoring,coloring agents, or combinations thereof. Delivery in an entericallycoated tablet, caplet, or capsule, to further enhance stability andprovide release in the intestinal tract to improve absorption, is thebest mode of administration currently contemplated.

Dosage

Dosage levels on the order of about 0.001 mg to about 100 mg perkilogram body weight of the active ingredient compounds or compositionsare useful in the treatment of the above conditions, with preferredlevels ranging from 200 mg per day to 1600 mg per day. The compounds andcompositions of the present inventive subject matter may usually begiven in two or three doses daily. Starting with a low dose (200-300 mg)twice daily and slowly working up to higher doses if needed is apreferred strategy. The amount of active ingredient that may be combinedwith the carrier materials to produce a single dosage form will varydepending upon the host treated and the particular mode ofadministration.

It is understood, however, that a specific dose level for anyparticular-patient will depend upon a variety of factors, including theactivity of the specific compound employed; the age, body weight,general health, sex and diet of the patient; the time of administration;the rate of excretion; drug combination; the severity of the particulardisorder being treated; and the form of administration. One of ordinaryskill in the art would appreciate the variability of such factors andwould be able to establish specific dose levels using no more thanroutine experimentation.

EXAMPLES

The following examples are illustrative of the present inventive subjectmatter and are not intended to be limitations thereon. Unless otherwiseindicated, all percentages are based upon 100% by weight of the finalcomposition.

Example 1 Preparation of the Inventive Compositions

The inventive compositions are prepared by methods known in the art, anddisclosed in Applicants' U.S. Pat. No. 6,387,416. The preparation of thecomponent elements of the inventive compositions is summarized asfollows:

The hydroalcoholic extract of ginger used in the inventive compositionsis preferably prepared as follows. The ginger rhizome, which ispreferably cryogenically ground to preserve heat sensitive components,is subjected to supercritical extraction to obtain: (i) an oil extract,referred to herein as “the supercritical extract” of ginger, containingdelicate lipophilic components, and (ii) an oil-free residue. Theoil-free residue is then extracted in a water/alcohol, preferablywater/ethanol, mixture composed of 60-80 parts alcohol and 40-20 partswater. The alcohol/water liquid is then evaporated off, leaving apowdered extract residue, referred to herein as “the hydroalcoholicextract” of ginger.

The composition of this invention will preferably contain thesupercritical extract and the hydroalcoholic extract of ginger at aweight ratio of preferably from about 0.9 to about 1.4 parts, morepreferably from about 1.1 to about 1.3 parts, most preferably about 1.17parts, of supercritical extract per 1 part post-supercriticalhydroalcoholic extract.

The supercritical extracts of ginger, rosemary, turmeric and oreganoused in the inventive compositions can be prepared according to knownsupercritical extraction methods, such as disclosed, e.g., in E. Stahl,K. W. Quirin, D. Gerard, Dense Gases for Extraction and Refining,Springer Verlag 4 1988, which is hereby incorporated by referenceherein.

The hydroalcoholic extracts of rosemary, turmeric, holy basil, greentea, huzhang, Chinese goldthread, barberry and Scutellaria baicalensisused in the inventive compositions can be prepared according toconventional hydroalcoholic extraction techniques. For example, thehydroalcoholic extracts can be prepared by extracting the plant portionin a water/alcohol (preferably water/ethanol) mixture (preferablycomposed of 60-80 parts alcohol and 40-20 parts water), and thenevaporating off the water/alcohol liquid, leaving a powdered extractresidue (referred to herein as “the hydroalcoholic extract”).

In the composition of this invention, the hydroalcoholic extract ofturmeric and the supercritical extract of turmeric will preferably bepresent at a weight ratio of preferably from about 8 to about 12 parts,more preferably from about 9 parts to about 11 parts, most preferablyabout 10 parts, of hydroalcoholic extract per 1 part of supercriticalextract.

The composition of this invention will preferably contain thesupercritical extract of rosemary and the hydroalcoholic extract ofrosemary at a weight ratio of preferably from about 1.6 to about 2.4parts, more preferably from about 1.8 to about 2.2 parts, mostpreferably about 2.0 parts, of supercritical extract per 1 part ofhydroalcoholic extract.

The hydroalcoholic extract of ginger used in the inventive compositionswill preferably contain from about 2.4% to about 3.6%, more preferablyfrom about 2.7% to about 3.3%, most preferably about 3.0%, by weight ofpungent compounds (e.g., shogaol).

The supercritical extract of ginger used in the inventive compositionswill contain preferably from about 24% to about 36%, more preferablyfrom about 27% to about 33%, most preferably about 30%, by weight ofpungent compounds (e.g., shogaol) and preferably from about 6.4% toabout 9.6%, more preferably from about 7.2% to about 8.8%, mostpreferably about 8%, by weight of zingiberene.

The supercritical extract of turmeric used in the inventive compositionswill contain preferably from about 36% to about 54%, more preferablyfrom about 40.5% to about 49.5%, most preferably about 45%, by weight ofturmerones.

The supercritical extract of rosemary used in the inventive compositionswill contain preferably from about 18.4% to about 27.6%, more preferablyfrom about 20.7% to about 25.3%, most preferably about 23%, by weight oftotal phenolic antioxidants (“TPA”).

The supercritical extract of oregano used in the inventive compositionswill contain preferably from about 0.64% to about 0.96%, more preferablyfrom about 0.72% to about 0.88%, most preferably about 0.8%, by weightof TPA.

The hydroalcoholic extract of turmeric used in the inventivecompositions will contain preferably from about 5.6% to about 8.4%, morepreferably from about 6.3% to about 7.7%, most preferably about 7%, byweight of curcumin.

The hydroalcoholic extract of rosemary used in the inventivecompositions will contain preferably from about 18.4% to about 27.6%,more preferably from about 20.7% to about 25.3%, most preferably about23%, by weight of TPA.

The hydroalcoholic extract of holy basil used in the inventivecompositions will contain preferably from about 1.6% to about 2.4%, morepreferably from about 1.8% to about 2.2%, most preferably about 2%, byweight of ursolic acid.

The hydroalcoholic extract of green tea used in the inventivecompositions will contain preferably from about 36% to about 54%, morepreferably from about 40.5% to about 49.5%, most preferably about 45%,by weight of polyphonies.

The hydroalcoholic extract of huzhang used in the inventive compositionswill contain preferably from about 6.4% to about 9.6%, more preferablyfrom about 7.2% to about 8.8%, most preferably about 8%, by weight ofresveratrol.

The hydroalcoholic extract of Chinese goldthread used in the inventivecompositions will contain preferably from about 4.8% to about 7.2%, morepreferably from about 5.4% to about 6.6%, most preferably about 6%, byweight of berberine.

The hydroalcoholic extract of barberry used in the inventivecompositions will contain preferably from about 4.8% to about 7.2%, morepreferably from about 5.4% to about 6.6%, most preferably about 6%, byweight of berberine.

Example 2 Effect of the Inventive Compositions on Prostate Cancer Cells

A series of dilutions of the inventive composition in DMSO wereprepared, and the dilutions were added to LNCaP growth medium so thatall doses tested had equivalent (0.1%) DMSO levels. Cell growth curveswere prepared by counting cells at 24, 48, and 72 hours, and werecompared to control cells treated at the same times with 0.1% DMSOalone. Apoptosis in these cultures was evaluated by Western blotanalysis of PARP cleavage and measurement of caspase-3 activity using acalorimetric substrate assay. Effects on purified COX-2 enzyme activitywas measured using a calorimetric assay, and effects on COX-2 proteinexpression was determined via Western blot analysis of protein extractsfrom treated cells. Activities were also compared to the effects ofpurified curcumin dissolved in DMSO, at levels equivalent to those thatwould be found in the inventive compositions at similar doses.

LNCaP cell growth was suppressed by the inventive compositions, and by72 hours there was a 78% reduction in cell number in treated cultures(7.9×10⁴ vs 3.53×10⁵ cells per well, p=0.01) compared to controls. PARPcleavage fragments were evident and caspase-3 activity was upregulated2-fold by 72 hour treatment, demonstrating an apoptotic effect that wasnot found in controls. COX-2 activity was also significantly decreasedin the presence of the inventive compositions, while equivalent doses ofcurcumin alone did not inhibit COX-2 in the assay utilized. COX-2protein expression in LNCaP cells was not affected. The results are ofthis example are shown in FIGS. 1-5.

These results demonstrate that the inventive compositions stronglysuppress LNCaP cells and induce apoptosis. These effects appear to bemore potent that those observed with curcumin alone, demonstrating asynergistic effect between the extracts used in the inventivecompositions.

Example 3 Effect of the Inventive Compositions on Pre-Malianant ProstateNeoplasia

A patient presents for treatment of a pre-malignant neoplasia of theprostate. An inventive composition is administered to said patient overa course of treatment lasting for several weeks, resulting in nosignificant side effects. The patient experiences a reversal in thegrowth of neoplastic cells and death of existing neoplastic cells,resulting in the neoplasia becoming undetectable.

Example 4 Effect of the Inventive Compositions on Prostate Epithelioma

A patient presents for treatment of a malignant stage B epithelioma ofthe prostate, confirmed by elevated PSA test, manual examination, andbiopsy of the tumor. An inventive composition is administered to saidpatient over a course of treatment lasting for several months, resultingin no significant side effects. The patient experiences a reversal inthe growth rate of tumor cells, death of existing tumor cells andreduction in tumor size, and no metastasis of the tumor. With continuingtreatment, the patient continues to exhibit no secondary symptoms ofprostate neoplasia, no long term side effects of the treatment, and nometastasis of the tumor.

The inventive subject matter being thus described, it will be obviousthat the same may be modified or varied in many ways. Such modificationsand variations are not to be regarded as a departure from the spirit andscope of the inventive subject matter and all such modifications andvariations are intended to be included within the scope of the followingclaims.

1-35. (canceled)
 36. A method for treating prostate neoplasia in asubject, comprising the step of administering an effective amount of acomposition to said subject to treat said prostate neoplasia, saidcomposition comprising, in combination: (a) therapeutically effectiveamounts of supercritical extracts of rosemary, turmeric, oregano andginger; therapeutically effective amounts of hydroalcoholic extracts ofholy basil, ginger, turmeric, Scutellaria baicalensis, rosemary, greentea, huzhang, Chinese goldthread, and barberry; and (b) atherapeutically effective amount of an antineoplastic agent selectedfrom the group consisting of mitoxantrone, doxorubicin, vinblastine,paclitaxel, docetaxel, estramustine phosphate, etoposide, carboplatin,vinorelbine, and a combination thereof, and provided that said prostateneoplasia is not prostatic intraepithelial neoplasia.
 37. The method ofclaim 36, wherein element (a) of said composition is administeredorally.
 38. The method of claim 37, wherein the orally administeredelement (a) of said composition is in the form of one or more capsules,one or more tablets, or one or more pills.
 39. The method of claim 36,wherein said composition is administered in a daily dosage of at leastabout 700 mg.
 40. The method of claim 36, wherein said composition isadministered on a daily basis for at least 4 weeks.
 41. A method fortreating at least one cancerous tumor of the prostate in a subject,comprising the step of administering an effective amount of acomposition to said subject to treat said tumor, said compositioncomprising, in combination: (a) therapeutically effective amounts ofsupercritical extracts of rosemary, turmeric, oregano and ginger;therapeutically effective amounts of hydroalcoholic extracts of holybasil, ginger, turmeric, Scutellaria baicalensis, rosemary, green tea,huzhang, Chinese goldthread, and barberry; and (b) a therapeuticallyeffective amount of an antineoplastic agent selected from the groupconsisting of mitoxantrone, doxorubicin, vinblastine, paclitaxel,docetaxel, estramustine phosphate, etoposide, carboplatin, vinorelbine,and a combination thereof.
 42. The method of claim 41, wherein element(a) of said composition is administered orally.
 43. The method of claim42, wherein the orally administered element (a) of said composition isin the form of one or more capsules, one or more tablets, or one or morepills.
 44. The method of claim 41, wherein said at least one canceroustumor is detected during surgery on the prostate of said subject, havingnot been felt by a physician on physical examination of said subject.45. The method of claim 41, wherein said at least one cancerous tumor isconfined to the prostate of said subject and is detected by a physicianon physical examination of said subject.
 46. The method of claim 41,wherein cancer related to said at least one cancerous tumor extendsbeyond the prostate capsule of said subject, but has not spread to lymphnodes in said subject.
 47. The method of claim 41, wherein cancerrelated to said at least one cancerous tumor is metastasized to regionallymph nodes or other parts of said subject.
 48. A method for minimizinga side effect associated with prostate neoplasia in a subject,comprising administering an effective amount of a composition to saidsubject to treat said side effect, said composition comprising, incombination: (a) therapeutically effective amounts of supercriticalextracts of rosemary, turmeric, oregano and ginger; therapeuticallyeffective amounts of hydroalcoholic extracts of holy basil, ginger,turmeric, Scutellaria baicalensis, rosemary, green tea, huzhang, Chinesegoldthread, and barberry; and (b) a therapeutically effective amount ofan antineoplastic agent selected from the group consisting ofmitoxantrone, doxorubicin, vinblastine, paclitaxel, docetaxel,estramustine phosphate, etoposide, carboplatin, vinorelbine, and acombination thereof, wherein said side effect is selected from the groupconsisting of disrupted sexual desire or performance on either atemporary or permanent basis, impotence, and urinary incontinence. 49.The method of claim 48, wherein element (a) of said composition isadministered orally.
 50. The method of claim 49, wherein the orallyadministered element (a) of said composition is in the form of one ormore capsules, one or more tablets, or one or more pills.
 51. The methodof claim 48, wherein said side effect so treated comprises disruptedsexual performance.
 52. A method for minimizing an effect associatedwith prostate neoplasia in a subject, comprising administering aneffective amount of a composition to said subject to minimize saideffect, said composition comprising, in combination: (a) therapeuticallyeffective amounts of supercritical extracts of rosemary, turmeric,oregano and ginger; therapeutically effective amounts of hydroalcoholicextracts of holy basil, ginger, turmeric, Scutellaria baicalensis,rosemary, green tea, huzhang, Chinese goldthread, and barberry; and (b)a therapeutically effective amount of an antineoplastic agent selectedfrom the group consisting of mitoxantrone, doxorubicin, vinblastine,paclitaxel, docetaxel, estramustine phosphate, etoposide, carboplatin,vinorelbine, and a combination thereof, wherein said effect is selectedfrom the group consisting of extensive monitoring for progression of thedisease and stress of illness.